Department of Paediatric Haematology, Oncology and Palliative Care, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom.
Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
Blood Adv. 2023 Feb 28;7(4):602-610. doi: 10.1182/bloodadvances.2022008802.
Part 1 results of the open-label, randomized, global phase 3 SPARKLE trial supported continued assessment of ibrutinib with either modified rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) in pediatric patients with relapsed/refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL). We report final results of Part 2 evaluating the efficacy of ibrutinib plus RICE or RVICI vs RICE/RVICI alone. Patients aged 1 to 30 years (initial diagnosis <18 years) were randomized 2:1 to receive ibrutinib with or without RICE/RVICI. Primary endpoint was event-free survival (EFS) based on independent committee-confirmed events. Fifty-one patients were enrolled. Median age was 15 years; Burkitt lymphoma, Burkitt leukemia, and Burkitt-like lymphoma (total: 45%) and diffuse large B-cell lymphoma/primary mediastinal B-cell lymphoma (51%) were the most common subtypes. At the preplanned interim analysis, median EFS was 6.1 vs 7.0 months with ibrutinib plus RICE/RVICI vs RICE/RVICI, respectively (hazard ratio, 0.9; 90% confidence interval, 0.5-1.6; P = .387); further enrollment was ceased. With ibrutinib plus RICE/RVICI vs RICE/RVICI, median overall survival was 14.1 vs 11.1 months, overall response rate was 69% vs 81%, and 46% vs 44% proceeded to stem cell transplantation. In both treatment arms, 100% of patients experienced grade ≥3 treatment-emergent adverse events. No EFS benefit was seen with ibrutinib. Salvage was generally poor in patients who received prior rituximab, regardless of treatment arm. No new safety signals were observed. Ibrutinib exposure in pediatric patients fell within the target range of exposure in adults. Trial is registered on www.clinicaltrials.gov (NCT02703272).
第一部分结果来自于开放标签、随机、全球性的 3 期 SPARKLE 试验，该试验支持在复发/难治性（R/R）成熟 B 细胞非霍奇金淋巴瘤（B-NHL）患儿中继续评估伊布替尼联合改良利妥昔单抗、异环磷酰胺、卡铂和依托泊苷（RICE）或利妥昔单抗、长春新碱、异环磷酰胺、卡铂、阿柔比星和地塞米松（RVICI），如果伊布替尼联合 RICE 或 RVICI 对比单独 RICE/RVICI 有效。我们报告了评估伊布替尼联合 RICE 或 RVICI 对比单独 RICE/RVICI 疗效的第二部分的最终结果。年龄 1 至 30 岁（初始诊断＜18 岁）的患者按 2:1 随机分组接受伊布替尼联合或不联合 RICE/RVICI。主要终点为独立委员会确认的事件的无事件生存（EFS）。共纳入 51 例患者。中位年龄为 15 岁；最常见的亚型为 Burkitt 淋巴瘤、Burkitt 白血病和 Burkitt 样淋巴瘤（总计：45%）和弥漫性大 B 细胞淋巴瘤/原发性纵隔 B 细胞淋巴瘤（51%）。在计划的中期分析中，伊布替尼联合 RICE/RVICI 对比 RICE/RVICI 的中位 EFS 分别为 6.1 个月和 7.0 个月（风险比，0.9；90%置信区间，0.5-1.6；P =.387）；进一步的入组停止。伊布替尼联合 RICE/RVICI 对比 RICE/RVICI 的中位总生存期分别为 14.1 个月和 11.1 个月，总缓解率分别为 69%和 81%，46%和 44%接受了干细胞移植。在两个治疗组中，均有 100%的患者发生了≥3 级治疗出现的不良事件。伊布替尼并未带来 EFS 获益。无论治疗组如何，先前接受过利妥昔单抗治疗的患者挽救治疗效果普遍较差。未观察到新的安全性信号。儿科患者的伊布替尼暴露量在成人的目标暴露量范围内。该试验已在 www.clinicaltrials.gov 上注册（NCT02703272）。
Zotero 插件
